Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry
Abstract Background The genomes of many insect and parasite species contain beta carbonic anhydrase (β-CA) protein coding sequences. The lack of β-CA proteins in mammals makes them interesting target proteins for inhibition in treatment of some infectious diseases and pests. Many insects and parasit...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2014-08-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/1756-3305-7-403 |
| _version_ | 1797811773766631424 |
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| author | Reza Zolfaghari Emameh Harlan Barker Vesa P Hytönen Martti E E Tolvanen Seppo Parkkila |
| author_facet | Reza Zolfaghari Emameh Harlan Barker Vesa P Hytönen Martti E E Tolvanen Seppo Parkkila |
| author_sort | Reza Zolfaghari Emameh |
| collection | DOAJ |
| description | Abstract Background The genomes of many insect and parasite species contain beta carbonic anhydrase (β-CA) protein coding sequences. The lack of β-CA proteins in mammals makes them interesting target proteins for inhibition in treatment of some infectious diseases and pests. Many insects and parasites represent important pests for agriculture and cause enormous economic damage worldwide. Meanwhile, pollution of the environment by old pesticides, emergence of strains resistant to them, and their off-target effects are major challenges for agriculture and society. Methods In this study, we analyzed a multiple sequence alignment of 31 β-CAs from insects, some parasites, and selected plant species relevant to agriculture and livestock husbandry. Using bioinformatics tools a phylogenetic tree was generated and the subcellular localizations and antigenic sites of each protein were predicted. Structural models for β-CAs of Ancylostoma caninum, Ascaris suum, Trichinella spiralis, and Entamoeba histolytica, were built using Pisum sativum and Mycobacterium tuberculosis β-CAs as templates. Results Six β-CAs of insects and parasites and six β-CAs of plants are predicted to be mitochondrial and chloroplastic, respectively, and thus may be involved in important metabolic functions. All 31 sequences showed the presence of the highly conserved β-CA active site sequence motifs, CXDXR and HXXC (C: cysteine, D: aspartic acid, R: arginine, H: histidine, X: any residue). We discovered that these two motifs are more antigenic than others. Homology models suggested that these motifs are mostly buried and thus not well accessible for recognition by antibodies. Conclusions The predicted mitochondrial localization of several β-CAs and hidden antigenic epitopes within the protein molecule, suggest that they may not be considered major targets for vaccines. Instead, they are promising candidate enzymes for small-molecule inhibitors which can easily penetrate the cell membrane. Based on current knowledge, we conclude that β-CAs are potential targets for development of small molecule pesticides or anti-parasitic agents with minimal side effects on vertebrates. |
| first_indexed | 2024-03-13T07:28:41Z |
| format | Article |
| id | doaj.art-ab15ce91fd71410aa17bac6110da2876 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-03-13T07:28:41Z |
| publishDate | 2014-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-ab15ce91fd71410aa17bac6110da28762023-06-04T11:15:31ZengBMCParasites & Vectors1756-33052014-08-017111110.1186/1756-3305-7-403Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandryReza Zolfaghari Emameh0Harlan Barker1Vesa P Hytönen2Martti E E Tolvanen3Seppo Parkkila4School of Medicine, University of TampereSchool of Medicine, University of TampereBioMediTech, University of TampereDepartment of Information Technology, University of TurkuSchool of Medicine, University of TampereAbstract Background The genomes of many insect and parasite species contain beta carbonic anhydrase (β-CA) protein coding sequences. The lack of β-CA proteins in mammals makes them interesting target proteins for inhibition in treatment of some infectious diseases and pests. Many insects and parasites represent important pests for agriculture and cause enormous economic damage worldwide. Meanwhile, pollution of the environment by old pesticides, emergence of strains resistant to them, and their off-target effects are major challenges for agriculture and society. Methods In this study, we analyzed a multiple sequence alignment of 31 β-CAs from insects, some parasites, and selected plant species relevant to agriculture and livestock husbandry. Using bioinformatics tools a phylogenetic tree was generated and the subcellular localizations and antigenic sites of each protein were predicted. Structural models for β-CAs of Ancylostoma caninum, Ascaris suum, Trichinella spiralis, and Entamoeba histolytica, were built using Pisum sativum and Mycobacterium tuberculosis β-CAs as templates. Results Six β-CAs of insects and parasites and six β-CAs of plants are predicted to be mitochondrial and chloroplastic, respectively, and thus may be involved in important metabolic functions. All 31 sequences showed the presence of the highly conserved β-CA active site sequence motifs, CXDXR and HXXC (C: cysteine, D: aspartic acid, R: arginine, H: histidine, X: any residue). We discovered that these two motifs are more antigenic than others. Homology models suggested that these motifs are mostly buried and thus not well accessible for recognition by antibodies. Conclusions The predicted mitochondrial localization of several β-CAs and hidden antigenic epitopes within the protein molecule, suggest that they may not be considered major targets for vaccines. Instead, they are promising candidate enzymes for small-molecule inhibitors which can easily penetrate the cell membrane. Based on current knowledge, we conclude that β-CAs are potential targets for development of small molecule pesticides or anti-parasitic agents with minimal side effects on vertebrates.https://doi.org/10.1186/1756-3305-7-403Beta carbonic anhydraseInhibitorsInsecticidesPesticidesAnti-parasitic agentsAgriculture |
| spellingShingle | Reza Zolfaghari Emameh Harlan Barker Vesa P Hytönen Martti E E Tolvanen Seppo Parkkila Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry Parasites & Vectors Beta carbonic anhydrase Inhibitors Insecticides Pesticides Anti-parasitic agents Agriculture |
| title | Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry |
| title_full | Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry |
| title_fullStr | Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry |
| title_full_unstemmed | Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry |
| title_short | Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry |
| title_sort | beta carbonic anhydrases novel targets for pesticides and anti parasitic agents in agriculture and livestock husbandry |
| topic | Beta carbonic anhydrase Inhibitors Insecticides Pesticides Anti-parasitic agents Agriculture |
| url | https://doi.org/10.1186/1756-3305-7-403 |
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